Prostaglandins may exhibit vasodilation or vasoconstriction, smooth muscle stimulation or depression. Prostaglandins of the E group, such as Prostaglandin E1 (PGE1) has been reported as having utility for the treatment of sexual erectile dysfunction when injected intracavernously as an aqueous solution in physiological saline, Mahmond et al., J. Urology 147:623-626 (1992), or applied topically. However, the prostaglandins, such as PGE1, are relatively insoluble in water, and are also relatively unstable. As a result, prostaglandin solutions for injection are prepared shortly prior to use, a relatively inconvenient expedient.
Attempts to stabilize PGE1 in aqueous systems by the use of α-cyclodextrin or β-cyclodextrin complexes have been reported. Wiese et al., J. Pharm. Sciences 80:153-156 (1991); Szejtli, J., “Industrial Applications of Cyclodextrins,” Inclusion Compounds III, Academic Press, London, England (1984), pp. 355-368. However, even the aqueous PGE1 preparations so-stabilized have a relatively short shelf life that limits their practical utilization.
It has now been found that the stability of prostaglandins of the E group can be substantially enhanced without sacrificing bioavailability by the use of specific non-aqueous pharmacologically acceptable compositions that can be stored in a separate compartment from a topical delivery vehicle and combined with the delivery vehicle just prior to use.